The Division of Research (DOR) of the Kaiser Permanente Medical Care Program (KPMCP) Northern California in collaboration with the Department of Medicine, Stanford University School of Medicine, and the Lawrence berkeley Laboratory, University of California, proposes to study the relation of insulin resistance to cardiovascular disease (CVD) and its risk factors across the spectrum of glucose tolerance in random sample of 400 adults drawn from more than 21,000 KPMCP members 40-69 years of age who took a Multiphasic Health Checkup in the preceding year. The sample will be stratified approximately equally on race (black/white), sex, and on fasting plasma glucose level at the checkup (<115, 116-140, and >140 mg/dl). Members will be invited to a two-part clinical examination at DOR that will include a two-hour oral glucose tolerance test and direct assessment of insulin sensitivity using the insulin suppression test. Glycosylated hemoglobin, fasting and postload insulin levels, fasting lipids, apolipoproteins, HDL and LDL subclasses, lipoprotein(a), fasting and postload plasma free fatty acids, clotting factors (fibrinogen, Factor VII, and plasminogen activator inhibitor) will be measured in all subjects. Free testosterone and sex hormone binding globulin would be measured in women only. Other tests include electrocardiographic, echocardiographic, and carotid ultrasonography examinations, anthropometry, arm/ankle blood pressures, and careful evaluation of dietary and physical activity patterns. With this information, we can directly examine independent associations of insulin resistance with other CVD risk factors in each sex, race, and glucose tolerance stratum, assess the possible contributions of insulin resistance and hyperglycemia to clinical and subclinical CVD, and search for cofactors that may modify insulin-resistance related risk in some populations. Lawrence Berkeley Laboratory, under Dr. Krauss, is also offering to serve as the central laboratory and will measure, or arrange to have measured, all lipids, insulin, and coagulation factors.